DNA And Prescriptive Drugs for Depression

"Psychiatric medicines make people feel horrible if you choose the wrong one."
"And they feel great if you choose the right one."
Dr. Jeremy Bruce, general practitioner, Cincinnati

"The differences [between haphazard drug prescriptions and prescriptions after genetic testing] are very small, and there's no reason to think you couldn't have done better by just following standard protocols, which are free."
"Metabolism is only a part of drug response, and even it is more determined by nongenetic factors."
"I'm not saying that drug metabolism doesn't matter. It's a question of degrees, it's a question of how much of somebody's response is determined by metabolism."
Dr. Bruce Cohen, director, Program for Neuropsychiatric Research, McLean Hospital, Massachusetts

"Over and over and over again studies show that patients who have 'particular' genetic defects have more toxicity, for example, than patients who don't [which could cause adverse reactions to a drug]."
Dr. Mary V. Relling, chair, pharmaceutical sciences department, St.Jude Children's Research Hospital

"I would say to the critics, 'Do you have any other suggestions right now when you have a person in your office and things don't seem to be working'?"
"I think that it [genetic testing in aiding antidepressant prescriptions] has a place at the present time."
"Maybe something else will come along that's better, but this is an important start."
Dr. Anthony Rothschild, professor of psychiatry, University of Massachusetts Medical School

Dr. Bruce, practising in Cincinnati, had any number of experiences where a patient would present with depression and he would prescribe an antidepressant, and refer the patient to a psychiatrist. The psychiatrist, observing that the first medication failed to help the patient, tried another, and then another and another yet, each time hoping that one of the drugs would end up working and the patient's depressed state would begin to lift.

Dr. Bruce treated his patients for depression in a time-honoured way, practised by all physicians in response to a patient's need for a mood-lifting therapy. He would initiate the patient on one antidepressant, switching to another until finally one of the drugs was proven to be of help. While he may have had the patience to follow through on the routine, some of the patients got fed up when nothing helped and would leave his practise in search of another doctor.

"They would usually be very angry", commented Dr. Bruce. Three years ago it occurred to him to approach the vexing problem in a different direction. When a patient who failed to respond well once one or two different antidepresssants were prescribed, he began making use of a company claiming it used an individual's genetics and matched the patient with the antidepressants based on their DNA results, most likely to lead to a successful outcome.

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The result was less than sterling, but it did hold out hope for some patients; the test's recommendations were of benefit to some patients, while not all. He has taken to offering the test to any of his patients presenting with depression, instead of prescribing the first antidepressant. The ensuing genetic report outlined the medications on a list of drugs unlikely to work with that genetic profile, and a list of patient-specific medications based on their DNA analysis.

The process, new to the profession, is called pharmacogenetics in the treatment of depression -- but not all health professionals believe in its efficacy. While Dr. Bruce feels the procedure has demonstrated some good results, there is a host of others who claim an absence of solid evidence indicating that pharmacogenetics works in reflection of the complexities of mental health treatment, is less than convincing.

The relation between genes and the manner in which a drug can affect the body have been validated by some laboratory tests, yet studies focusing on whether the use of that information will lead to improved results for patients remain inconclusive. Studies thus far have failed to demonstrate that genetic testing in the selection of antidepressants leads to better outcomes for patients. The holdup? Genetic testing comes with a price tag from $100 to over $2000.

Dr. Cohen points out that the genetics tests focus on variations in genetic metabolism and how that affects the manner in which a person's body will process a drug where faster metabolism may lead to lower drug levels in the body, and slower metabolism can cause higher levels of drugs. Nothing is ever as simple as it seems; age, diet and other substances in the body have a major influence on drug processing, as well.

Reviews of published research provide prescribing guidelines which advise how to use genetic information already available, rather than calling for genetic tests to be ordered. And it is that already available genetic information that the Clinical Pharmacogenetics Implementation Consortium uses to rank the strength of various gene-drug pairings. Dr. Relling who co-founded the Consortium feels that genes dominate other factors such as age and diet.

Studies show a strong relationship between a gene and a drug which should be sufficiently useful to support prescribing guidelines, according to Dr. Relling, while Dr. Cohen feels that simply observing a relationship on the genetic level leaves out other important indexes, that studies are needed to prove patients actually experience improved outcomes with treatment guided by genetics.

In November, the U.S. Food and Drug Administration released a statement with the warning to patients and doctors that caution is required on genetic testing that has not been approved by the FDA, inclusive of those meant to guide the prescribing of antidepressants. And Dr. Rothschild feels such testing should be considered one tool in the depression-treating toolbox, most particularly where patients failed to respond to medication.

Your doctor may use cytochrome P450 (CYP450) tests to help determine how your body processes (metabolizes) a drug. The human body uses cytochrome P450 enzymes to process medications. Because of inherited (genetic) traits that cause variations in these enzymes, medications may affect each person differently.
Drug-gene testing — also called pharmacogenomics or pharmacogenetics — is the study of how genes affect your body's response to medication. Tests look for changes or variations in these genes that determine whether a medication could be an effective treatment for you or whether you could have side effects from a specific medication.
The cytochrome P450 enzyme includes the CYP2D6 enzyme, which processes many antidepressants and antipsychotic medications. By checking your DNA for certain gene variations, CYP450 tests can offer clues about how your body may respond to a particular antidepressant. CYP450 tests can also identify variations in other enzymes, such as the CYP2C19 enzyme.
Mayo Clinic